Safety and efficacy of inhaled pegylated adrenomedullin (PEG-ADM) in patients suffering from Acute Respiratory Distress Syndrome (ARDS): a double-blind, randomized, placebo-controlled, multicenter Phase 2a/b clinical trial

Phase 2

Completed

• Conditions: Acute Respiratory Distress Syndrome; 10024967

• Registration Number: NL-OMON51280
• Lead Sponsor: Bayer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 35

Inclusion Criteria

1. >=18 years of age at the time of inclusion into study.
2. Invasively mechanically ventilated ARDS patients (diagnosed according to
Berlin definition of ARDS, including PEEP of >=5 cm H²O, X-ray (or CT scan)
indicative of ARDS: bilateral opacities not fully explained by cardiac failure,
fluid overload, lobar/lung collapse, effusions or nodules).
3. Initial diagnosis of mild, moderate or severe ARDS prior to study inclusion,
with acute onset of ARDS within 1 week after suspected trigger factor of
a. Pneumonia
b. Aspiration
c. Sepsis
d. Pancreatitis
4. Prior to randomization, hypoxemia with PaO²:FiO² <=300 mmHg continuously
observed for a period of >=4 hours (with values of >=2 arterial blood gas [ABG]
analyses during that time, with the last value obtained timely (generally <=3
hours) prior to randomization), under ventilation with minimum PEEP >=8 cm H²O.
5. Time from first meeting the last diagnostic ARDS criterion (Berlin criteria)
to randomization must be <=48 hours.
6. For Study Part A: ARDS patients for whom measurements of extra-vascular lung
water are regarded as medically indicated by the treating physician, and these
measurements are planned as part of their clinical care, from Study Day 1 up to
Study Day 7 (if then still intubated).
7. Male and non-pregnant female
8. Informed consent of capable patient or, in case of patient being incapable
of giving informed consent, consent for study inclusion will be sought
according to applicable laws and regulations.

Exclusion Criteria

Medical Conditions
1. Any value of a PaO2:FiO2 ratio >300 mmHg within a time interval of 4
hours before randomization
2. Rescue therapy according to Section 6.5.1 (e.g. inhalation of nitric oxide
gas and/or inhalation of prostacyclin analogues, or ECMO/ECCO2R) already
initiated at screening and/or Study Day 1 (prior to first dose of the study
intervention)
3. Moribund participants not expected to survive 24 hours (clinical decision)
4. Expected duration of invasive mechanical ventilation less than 48 hours
(clinical decision)
5. History of co-morbidities requiring long-term/home oxygen use (e.g. severe
chronic obstructive pulmonary disease [COPD], pulmonary fibrosis) or
non-invasive ventilation (except for sleep apnea management), or making weaning
per se improbable (e.g. ALS, muscular dystrophy)
6. Smoke inhalation injury, extensive burns or trauma/head injury as
concomitant condition
7. History of pneumectomy, lung lobectomy or lung transplant
8. Diffuse alveolar hemorrhage from vasculitis
9. Current lung malignancy (incl. lung metastasis), or other malignancy
requiring chemotherapy or radiation within the last month
10. Chronic kidney disease with a history of renal replacement therapy (e.g.
dialysis)
11. Chronic liver disease Child-Pugh Class C
12. Chronic heart failure NYHA IV
13. Known hypersensitivity to polyethylenglycol (PEG, Macrogol)
14. Diagnosis of COVID-19 pneumonia within 6 weeks prior to study inclusion.
History of SARS-CoV-2 infection (positive test based on nucleic acid
amplification technology or positive antigen test) without COVID-19 pneumonia
does not exclude patients (see also Section 8.2.6)

Prior/Concurrent Clinical Study Experience
15. Plan to participate or past participation (within 30 days prior to Study
Day 1) in other interventional studies involving pharmacological interventions,
or biological or cell therapy interventions.
Participation in other interventional studies that study modifications of
supportive care regimens or similar objectives may be possible if the
intervention in question would be regarded not to endanger outcome assessments
or supportive care recommendations described in this protocol. Investigator and
sponsor assess the implications of such a study; if no mutual agreement is
reached, the patient is to be excluded.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Ventilator-free survival (VFS, proportion of participants alive and off<br /><br>invasive mechanical ventilation) at Study Day 28</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• All-cause mortality at Study Day 28, Study Day 60 and Study Day 90<br /><br>• Proportion of participants who still require invasive mechanical ventilation<br /><br>support at Study Day 28 and Study Day 60<br /><br>• Ventilator-free days (VFDs) within Study Day 28 and Study Day 60<br /><br>• Ventilator-free survival at Study Day 60<br /><br>• Integrated analysis on Ventilator-free survival at Study Day 28 and 60,<br /><br>involving all participants from Part A and Part B</p><br>